Bioinspired Synthesis of Curtachalasin A and Δ6,12-Curtachalasin N Enabled by Tandem Transannular Epoxyalkene Cyclization and α-Ketol Rearrangement.

Biomimetic syntheses of curtachalasin A (1) and Δ6,12-curtachalasin N (12), a highly oxidized rearranged cytochalasin-type featuring a novel 5/6/6/6 tetracyclic scaffold converted from naturally abundant cytochalasin D containing a 5/6/11 tricyclic skeleton, were first achieved efficiently in three and four steps, respectively. The conversion route features three pivotal transformations involving selective Prilezhaev epoxidation, acid-mediated tandem transannular epoxyalkene cyclization, and a subsequent spontaneous α-ketol rearrangement. This work provides an efficient approach to access the naturally occurring scarce curtachalasin A, paving the way for the syntheses of other members of the curtachalasins family and revealing the potential biosynthetic relationship between cytochalasins and curtachalasins in a chemical perspective.